The objective of this project is to study the role of prostaglandins in the regulation of utero-placental blood flow and in hypertensive disease of pregnancy (toxemia). In anesthetized monkeys, the effects of angiotensin-11 and indomethacin have been recorded on uterine artery blood flow and prostaglandin output by the uterus during the last trimester of pregnancy. It is planned to study the response to hypoxia and infusion of estradiol in terms of uterine artery blood flow and uterine production of prostaglandins. The principal analytic method is radioimmunoassay of prostaglandins. To overcome the problem of rapid metabolism of prostaglandins, an assay is being developed for the major circulating metabolite, 13,14-dihydro-15-keto prostaglandin E2. The synthesis of prostaglandins by trophoblastic cells is being studied in vitro utilizing a cell suspension technique.